Alpha-fetoprotein (AFP) is an embryo specific serum alpha-globulin glycoprotein that is synthesized in the fetal yolk sac and circulates through the serum of pregnant women (G.l. Abelev 1971). In the last several decades, clinical researchers have investigated the potential anti-estrogen and anti-breast cancer activities of AFP (Jacobson et al. 1990). A number of studies have since shown its effectiveness as a therapeutic agent to treat estrogen-dependent breast cancer, as well as its ability to prevent pre-malignant foci from developing into breast cancer. Specifically, these studies indicate that alpha-fetoprotein (AFP) interferes with estrogen-dependent responses, including the growth- promoting effects of estrogen on breast cancer (Bennett et al. 1998). U.S. Pat. No. 5,674,842 and U.S. Pat. No. 5,707,963 relate to a 34-amino acid peptide derived from alpha-fetoprotein that was shown to exhibit anti-estrotrophic activity. More recently, an 8-amino acid stretch of AFP (EMTPVNPG) (SEQ ID NO: 1), referred to as peptide P472-2, has been identified as possessing antiestrotrophic activity (Mesfin et al. 2000). Furthermore, U.S. Pat. No. 6,818,741 describes a peptide of eight to twenty amino acids, including a cyclic peptide (9-mer) that is useful in reducing estrogen-stimulated growth of cells.
Previous efforts to identify a peptide under eight residues resulted in the loss of anti-estrotrophic activity (DeFreest et al. 2004.) To date, the specific binding mechanism of AFP and of P472-2 is not known, making rational development of lead compounds difficult.